A new study published in The Journal of Infectious Diseases was based on the hypothesis that tetrahydrobiopterin (BH4) and BH4-dependent neurotransmitters would be low in cerebrospinal fluid (CSF) in cerebral malaria (CM).

This was a prospective study that recruited Tanzanian children with CM and those with non-malaria central nervous system conditions (NMC). CSF levels of BH4, neopterin and BH4-dependent neurotransmitter metabolites, 3-O-methyldopa, homovanillic acid and 5-hydroxyindoleacetate were measured, and age-adjusted z-scores were derived using published reference ranges.

The results revealed that CSF BH4 was elevated in CM patients compared to NMC patients. Whereas, neopterin was increased in CM, and a cut-off at the upper limit of normal (60 nmol/L) was 100% sensitive for CM. Meanwhile, the overall neurotransmitter metabolite levels were preserved. It was observed that a higher CSF BH4:BH2 ratio was associated with increased odds of survival.

Despite low systemic BH4, CSF BH4 was elevated and associated with increased odds of survival in CM. Thus, coma in malaria is not explained by deficiency of BH4-dependent neurotransmitters. 

Source: The Journal of Infectious Diseases. 2021 Feb 22;jiab086. doi: 10.1093/infdis/jiab086.